Evidence is avilable showing that cadmium is an industrial contaminant to which human exposure has increased. Since the establishment of safety levels for organism exposure requires input from various disciplines this proposal addresses the question of how the immune system is affected. A fully competent immune system is necessary for health and will be assessed in terms of selected functional immune assays, in groups of normal control rats and rats injected intraperitoneally with three doses weekly of 0.200 mg Cd2 ion/Kg body weight. With this dosage, 200 micrograms CD2 ion/g kidney tissue will be achieved in 6-8 months as indicated from a pilot study and has significance in reported literature as the concentration that just precedes nephrotoxicity. The primary and secondary responses to SRBC and BSA will be measured in treated and control groups at monthly intervals, using the plaque and Farr assays for humoral immunity and mitogen and MLC assays for cellular immunity. Assessment of transplantation immunity, circulating and membrane bound immunoglobulin and macrophage function in phagocytosis and lymphokine (MIF) production will be accomplished in mice receiving Cd2 ion similar to the treatment of the rats. Use of two species in which conditions are better known and also allows more general conclusions from two rather than one species. Another potentially detrimental effect of metal exposure may be approached by applying the RIA which has recently been developed in this laboratory. The present RIA has a sensitivity of detecting as low as 150 picograms of Cd-thionein. There is critical need for more information about this metal-protein metabolite in vivo since both protective and toxic roles have been ascribed to it. The possible existence of specific autologous immune complexes in the circulation and/or in tissues resulting from the presence of this protein will be investigated. Following dissociation-isolation of these complexes, identification of specific antigen and antibody will be achieved by the RIA.